Serum amyloid P component (SAP) is a conserved, constitutively-expressed, plasma protein and member of the pentraxin family of secreted pattern recognition receptors. It is present in all individuals at concentrations of 30 to 50 mg/L, and was first discovered in 1965 as a ubiquitous constituent of amyloid plaques. Its physiological function remains unclear despite considerable work to elucidate its pathological role. SAP has been identified as the only serum protein that exhibits calcium-dependent DNA-binding and has been shown to bind and solubilise native long chromatin. Due to its abundance in the serum it has been suggested that SAP’s normal role may be as a scavenger of extracellular DNA. However, there is very little information regarding the precise molecular nature of this interaction. Several biophysical methods were employed to investigate the affinity, stoichiometry, specificity and structure of the SAP-DNA interaction. SAP was found to bind with high affinity to double stranded DNA of 25 bp or longer, regardless of sequence, although binding is not entirely sequence independent. Mutational analysis using HEK 293 cell expressed recombinant protein has identified a number of positively charged amino acids that play a key role in the formation of the complex. The stoichiometry of SAP-DNA binding has been shown to be complicated, with little evidence for the formation of a discrete complex, but rather an indication that multiple SAP molecules decorate longer DNA strands. This may explain the difficulties in obtaining a crystal structure of the complex. SAP has also been shown to bind to nucleosome core particles, albeit with significantly weaker affinity than to naked DNA. The apparent promiscuity of SAP-DNA binding appears to support claims that SAP acts as a serum DNA scavenger, providing further evidence that SAP’s main physiological role is in the prevention of autoimmune reactions against nuclear material.